Endometrioid Ovarian Carcinoma in a Premenarchal Girl: Report of a Case

GYNECOLOGIC ONCOLOGY ARTICLE NO.

67, 222–225 (1997)

GO974868

CASE REPORT Endometrioid Ovarian Carcinoma in a Premenarchal Girl: Report of a Case1 Daniel Fink, M.D.,*,2 Steven C. Plaxe, M.D.,* Joseph F. Brown, M.D., and Rebecca N. Baergen, M.D. Department of Pathology and *Department of Reproductive Medicine and the Cancer Center, University of California at San Diego, La Jolla, California 92093 Received May 15, 1997

In children and adolescents, ovarian neoplasmas are predominantly germ cell and sex cord stromal tumors. Carcinomas are quite rare, and, in particular, endometrioid adenocarcinomas are extremely rare in this age group. We report the case of a 13-yearold girl with FIGO stage I, grade I endometrioid adenocarcinoma of the ovary. To our knowledge this is the first report of an endometrioid carcinoma of the ovary occuring in the premenarchal age group and only the second case reported before age 15. Our patient has been treated by conservative surgery without postoperative chemotherapy. Menarche occured 3 months after surgery. Twelve months after surgery she is free of disease. © 1997 Academic Press

INTRODUCTION Epithelial ovarian cancer is the leading cause of death among gynecologic malignancies. The incidence of ovarian cancer increases with age from 3 per 100,000 in women less than 30 years of age to 54.4 per 100,000 in women between the ages of 70 – 85 years [1]. In children and adolescents ovarian neoplasmas are predominantly germ cell and sex cord stromal tumors, with carcinomas constituting a minority of cases. In patients less than 25 years of age the endometrioid cell type is underrepresented with an incidence of 5% of all carcinomas compared to an incidence of 15–20% in all age groups [2]. One case of endometrioid carcinoma in a 11-year-old child has been reported with menarche occuring 5 months prior to presentation [3]. To our knowledge, this report of a 13-year-old girl with FIGO stage I, grade I endometrioid adenocarcinoma of the ovary describes the first case of an endometrioid carcinoma of the ovary occuring in the premenarchal age group and only the second case reported before age 15. 1 This work was supported in part by Fellowship Awards from the EMDO Stiftung, Zurich, and the Holderbank Stiftung to D.F. 2 To whom correspondence should be addressed at the Cancer Center 0058, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0058. Fax: (619) 822-1111.

0090-8258/97 $25.00 Copyright © 1997 by Academic Press All rights of reproduction in any form reserved.

CASE REPORT A 13-year-old white female presented with a 2-month history of abdominal swelling. She had light spotting 1 year prior to presentation and then no subsequent vaginal bleeding. Her past medical history was unremarkable and the system review was negative. A careful family history revealed no evidence of breast or ovarian cancer in any first degree relative. Physical examination revealed a child in otherwise good health with a distended abdomen. Transabdominal pelvic and endovaginal sonography suggested massive ascites present throughout the abdominal cavity and a 14 3 16 cm mass in the left adnexa. Computerized tomography confirmed the sonographic findings. The chest X ray was normal. Serum CA-125 was elevated to 303 U/ml (normal ,35 U/ml) and CEA to 121 ng/ml (normal ,2.5 ng/ml). Serum AFP and b-hCG were negative. Serum LDH was not elevated. At laparotomy, an 18-cm smooth encapsulated left ovarian tumor was found. There was a yellowish-brown tinge to all peritoneal surfaces. The rest of the abdomen including the right adnexa and the uterus was explored and found to be normal. Frozen sections revealed a papillary neoplasm. A left salpingo-oophorectomy, an infracolic omentectomy, periaortic and left pelvic lymphadenectomies, and multiple peritoneal biopsies were performed. Gross pathologic examination showed a 280-g mass measuring 18 3 14 3 9 cm (Fig. 1). The mass was encapsulated and the cut section revealed uniform, tannish-yellow soft tissue with focal areas of necrosis. Microscopic examination revealed a papillary tumor consisting of elongated, somewhat thin papillae lined by columnar epithelial cells with mild nuclear atypia. Pseudostratification and true stratification of the nuclei was seen and mitotic figures were easily identified. The histologic appearance was quite uniform throughout the tumor and was consistent with a well differentiated (FIGO grade I) endometrioid adenocarcinoma (Fig. 2). Immunohistochemistry was performed in the usual way to confirm the epithelial nature of the tumor and to rule out other more common papillary tumors in

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FIG. 1.

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Cut surface of the 18-cm, 280-g ovarian tumor.

this age group such as germ cell tumors including yolk sac tumor and struma ovarii with papillary adenocarcinoma as well as sex cord stromal tumors. Antibodies against cytokeratin (AE1/AE3 cocktail), epithelial membrane antigen, vimentin, alpha-fetoprotein, human chorionic gonadotropin, placental alkaline phosphatase, and thyroglobulin were used (all antibodies from DAKO Co., Carpinteria, CA). The tumor was strongly positive for cytokeratin and epithelial membrane antigen and clearly negative for all the remaining markers, confirming epithelial differentiation in the tumor. The peritoneal fluid samples were cytologically negative. The omentum, peritoneal biopsies, and the left pelvic and periaortic lymph nodes showed reactive mesothelial hyperplasia and inflammatory changes but no evidence of malignancy. Therefore, the clinicopathologic staging was FIGO stage IA. No postoperative chemotherapy was administered. Follow-up consisted of bimonthly physical examinations, serum CA-125, and pelvic ultrasounds every 6 months. Two months after surgery serum CA-125 was 23 U/ml (normal ,35 U/ml). Menarche occured 3 months after surgery. Twelve months after surgery the patient is free of disease. DISCUSSION It is clear that neoplasmas derived from the ovarian surface epithelium constitute a far smaller proportion of ovarian tu-

mors in children than in adults [2]. This supports the widely accepted pathogenetic mechanism of ‘‘incessant ovulation’’ as a cause of ovarian epithelial transformation. Repetitive trauma on the ovarian surface due to cyclic ovulation, as well as the exposure of the surface epithelium to the estrogen-rich follicular fluid, may produce abberant proliferation and subsequent malignant transformation [4]. Although carcinomas are rare in patients less than 15 years of age, cases have been reported, but these have been mostly serous and mucinous carcinomas. Blom et al. [5] reported the case of a 4-year-old girl with a serous ovarian carcinoma, treated with radical surgery. Hernandez et al. [6] described a stage Ia mucinous cystadenocarcinoma in a 10-year-old child. After conservative surgery, she received adjuvant chemotherapy and subsequently had normal puberty. Du Toit et al. [7] recently presented the case of a stage IIIc mucinous cystadenocarcinoma in a 10-year-old premenarchal girl which resulted in an intestinal obstruction. The outcome was fatal despite multimodal therapy, which included ablative surgery and platinum-containing chemotherapy. Endometrioid carcinomas in this very young age group are even rarer. Byrd [3] reported a 11-year-old child presenting at diagnosis with a surgically unresectable stage III, poorly differentiated endometrioid ovarian carcinoma. Menarche had occurred 5 months prior to presentation. In the premenarchal age

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FIG. 2. Photomicrograph of the tumor showing long slender papillae lined by tall columnar pseudostratified cells characteristic of endometrioid adenocarcinoma. Hematoxylin and eosin; original magnification, (A) 20X, (B) 200X.

group, only serous and mucinous ovarian carcinomas have previously been reported. We report the first case of an endometrioid carcinoma of the ovary occuring in this age group. Endometrioid carcinoma is associated with pelvic endometriosis in 28% of cases [8] and in some cases, origin from endometriosis can be documented. Controversy exists regarding the pathogenesis of endometriosis. The principal mechanisms suggested include: (1) lymphatic or hematogenous dissemination; (2) retrograde menstruation and implantation from the uterine endometrium; or (3) metaplasia of the ovarian surface epithelia to resemble the tubular glands of the endometrium. One can postulate that the rarity of endometrioid carcinomas in premenarchal girls may be related to the pathogenesis of endometriosis. Epithelial ovarian carcinoma patients age 30 years or younger have a more favorable prognosis because of a higher rate of early-stage and low-grade tumors [9]. In a study by Morris et al. [10], 75% of the 12 cases of serous and mucinous neoplasms in the age group 10–14 years presented as stage I. The 10-year survival rate for stage I disease was 100%. The difference in survival as a function of age could also be explained on the basis of other biologic host-related factors. It has been speculated that the hormonal milieu of women of reproductive age could make them less vulnerable to the progression of malignant disease. In particular, it has been hypothesized that the presence of

circulating progesterone in younger women could prevent the adverse effect of estrogens in the process of initiation and progression of metastatic disease [11]. Since experience with epithelial ovarian carcinoma in young girls is so limited, no definite conclusions regarding treatment can be drawn from the literature. Individualization of therapy based on treatment regimens designed for adults with such neoplasms is necessary until more data are obtained regarding similarities and/or differences in behavior between epithelial tumors occuring in children and in adults. Because early-stage and low-grade tumors are frequent in these young patients, conservative surgery may be performed whenever possible to preserve fertility. If the uterus and contralateral ovary appear uninvolved, then unilateral salpingo-oophorectomy with surgical staging is generally recommended; if both ovaries are involved, then uterine preservation for in vitro fertilization may be considered. REFERENCES 1. Yancik R: Ovarian cancer: age contrasts in incidence, histology, disease stage at diagnosis, and mortality. Cancer 71:517–523, 1993 2. Rodriguez M, Nguyen HN, Averette HE, Steren AJ, Penalver MA, Harrison T, Sevin BU: National survey of ovarian carcinoma XII. Cancer 73:1245–1250, 1994

CASE REPORT 3. Byrd R: Ovarian endometrioid carcinoma in an eleven-year-old child. Med Pediatr Oncol 7:219 –224, 1979 4. Fathalla MF: Incessant ovulation—a factor in ovarian neoplasia? Lancet 2:163, 1971 5. Blom GP, Torkildsen EM: Ovarian cystadenocarcinoma in a 4-year-old girl: Report of a case and review of the literature. Gynecol Oncol 13:242– 246, 1982 6. Hernandez E, Rosenshein NB, Parmley TH: Mucinous cystadenocarcinoma in a premenarchal girl. South Med J 75:1265–1267, 1982 7. Du Toit GC, Moore SW: Mucinous ovarian adenocarcinoma in the premenarchal patient: a case presentation. Int J Gynecol Cancer 7:166–168, 1997

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8. Russell P: The pathological assessment of ovarian neoplasms. Pathology 11:493–532, 1979 9. Plaxe SC, Braly PS, Freddo JL, McClay E, Kirmani S, Howell SB: Profiles of women age 30 –39 and age less than 30 with epithelial ovarian cancer. Obstet Gynecol 81:651– 654, 1993 10. Morris HB, La Vecchia C, Draper GJ: Malignant epithelial tumors of the ovary in childhood: A clinicopathological study of 13 cases in Great Britain 1962–1978. Gynecol Oncol 19:290 –297, 1984 11. Badwe RA, Patil PK, Bhansali MS, Mistry RC, Juvekar RR, Desai PB: Impact of age and sex on survival after curative resection for carcinoma of the esophagus. Cancer 74:2425–2429, 1994